The T cell response to rapidly evolving HIV antigens

描述(由申请人提供)：抗病毒CD8+T细胞在艾滋病毒复制的初始控制中发挥重要作用，并可能有助于推迟艾滋病毒感染者的艾滋病发作。为了了解抗病毒CD8+T细胞在免疫保护中的作用，有必要全面研究HIV感染者CD8+T细胞的特异性。实现这一目标的一个主要障碍是来自不同个体的艾滋病毒临床分离株之间高度的遗传变异。目前大多数筛选T细胞特异性的技术依赖于代表一致序列的参考菌株抗原或合成肽。由于检测抗原和自体病毒之间的遗传差异，这些方法可能低估了T细胞反应。这项建议描述了一种基于用合成的mRNA转染抗原提呈细胞的方法，用于有效地筛选患者CDS+T细胞对自体HIV抗原的反应。这种方法将被用来比较慢性HIV感染中T细胞对自体抗原和共同抗原的反应。

DESCRIPTION (provided by applicant): Antiviral CD8+ T cells play an important role in initial control of HIV replication and presumably help delay the onset of AIDS in HIV infected individuals. In order to understand the role of antiviral CD8+ T cells in immune protection, it will be necessary to comprehensively characterize the specificities CD8+ T cells in HIV-infected patients. A major obstacle to this goal is the high degree of genetic variability among HIV clinical isolates from different individuals. Most current techniques to screen T cell specificities rely on reference strain antigens or synthetic peptides representing a consensus sequence. These methods may underestimate T cell response due to genetic divergence between the assay antigen and autologous virus. This proposal describes an approach, based on transfection of antigen presenting cells with synthetic mRNA, for efficient screening of patient CDS+ T cell responses to autologous HIV antigens. This method will be used to compare the T cell responses to autologous and consensus antigens in chronic HIV infection.